963 research outputs found
Multitasking Roles of the Mammalian Deacetylase SIRT6
No full textSirtuins (SIRT) are highly conserved proteins first described as nicotinamide adenine dinucleotide (NAD+)-dependent type III histone deacetylases. They are the mammalian homologs of the SIR2 gene found in yeast. Seven homologs (SIRT1–7) have been described, all sharing an NAD+ binding catalytic domain comprising 275 amino acids and variable N and C termini. This difference in their terminal domains dictates distant roles and cellular localization of the members of the sirtuin family. In this review, we will focus on the chromatin deacetylase SIRT6, a multitasking protein with various roles in metabolism, development, DNA repair, and cancer. We will provide current knowledge in the context of its structure, enzymatic activity, and regulation. We will discuss its role in genomic stability and DNA repair, metabolism, and development. Finally, we will review SIRT6’s involvement in several diseases
SIRT3 deacetylase: the Jekyll and Hyde sirtuin
No full textPost‐translational modifications have crucial roles in regulating the functions of many eukaryotic proteins. Among them, lysine acetylation has been traditionally studied in the context of nuclear histone modifications, and was one of the first to be described as part of the ‘histone code’ hypothesis (Kim et al, 2006). More recently, work from several groups has demonstrated that lysine acetylation also modulates the activity of several non‐histone proteins. In this context, this modification seems particularly abundant on mitochondrial proteins (Schwer et al, 2009). However, the way in which acetylation influences enzyme function and metabolic reprogramming in pathological states remains unknown. In an article published online this month in EMBO reports, Sack and colleagues shed new light on the role of mitochondrial SIRT3 deacetylase during paracetamol‐induced toxicity, describing the mitochondrial protein aldehyde dehydrogenase 2 (ALDH2) as a new target of SIRT3, and a protective role for protein acetylation in this context.Fil: Silberman, Dafne Magali. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mostoslavsky, Raul. Harvard Medical School; Estados Unido
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Friends, Family gather at Dr. Clotilde Garcia's home honoring Raul Morin (photograph)
No full textFriends, Family gather at Dr. Clotilde Garcia's home honoring Raul Morin. Author of the book “Among the Valient.
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Raul Morin, author of 'Among the Valiant' shakes hands with Dr. Hector P. Garcia (photograph)
No full text(L. to R.): Raul Morin, author of 'Among the Valiant' shakes hands with Dr. Hector P. Garcia
Raul and his family : psychoanalytic considerations
No full textO autor revisa algumas contribuições psicanalíticas para a compreensão dos comportamentos violentos. Utilizando tais dados, procura examinar o caso de Raul e sua família e entender, do ponto de vista psicanalítico, as motivações do paciente e de seus familiares, bem como da equipe que os atendeu.The author revises some psychoanalytic contributions for the understanding of violent behaviour. From these data, the author examines Raul and his family’s case and tries to understand, from the psychoanalytic perspective, their motivations, as well as the staff’s that was responsible for their care
Transcreazione di immagini e parole. "Gli amori di mia madre" di Peter Schneider
No full textIl saggio analizza Gli amori di mia madre di Peter Schneider come esempio paradigmatico di transcreazione, un processo che intreccia traduzione, reinvenzione e narrazione nella ricostruzione del passato. Il romanzo nasce dall’incontro dello scrittore con le fotografie e, soprattutto, con le lettere scritte dalla madre Annalise durante il nazismo e il dopoguerra, conservate per decenni in una scatola e redatte in alfabeto Sütterlin. La loro decifrazione, resa possibile grazie all’intervento della traduttrice Gisela Deus, avvia un percorso di reinterpretazione emotiva e storica, in cui Schneider rielabora la vita della madre e la propria infanzia.
Attraverso la sinergia fra immagini, testimonianze epistolari e memoria soggettiva, l’autore compie un atto di riconciliazione con la figura materna, rivelandone la complessità affettiva e biografica: una donna segnata dalla guerra, da passioni irrisolte e da un amore forse reale, forse immaginato. Il saggio mostra come la transcreazione diventi un dispositivo narrativo che sovverte il confine tra documento e finzione, tra individuale e collettivo, offrendo un affresco della Germania devastata dal conflitto e, insieme, un’indagine sul ruolo creativo del traduttore, sulla fallibilità della memoria e sulla possibilità di trasformare il passato in racconto. Il romanzo emerge così come un’opera di ricomposizione affettiva, storica e linguistica, capace di opporre alla distruzione solo la forza dei legami umani e della scrittura.The essay examines Peter Schneider’s "Die Liebe meiner Mutter" as a paradigmatic example of transcreation, a narrative process that blends translation, reinvention, and reinterpretation in order to reconstruct the past. The novel originates from Schneider’s encounter with family photographs and, above all, with the letters written by his mother Annalise during Nazism and the early postwar years, preserved for decades in a cardboard box and written in the now-obsolete Sütterlin script. Their deciphering—made possible through the collaboration of translator Gisela Deus—initiates a path of emotional and historical reinterpretation in which Schneider revisits his mother’s life and his own childhood.
Through the interplay of images, epistolary material, and subjective memory, the author undertakes a profound act of reconciliation with his mother, revealing her emotional and biographical complexity: a woman marked by war, unfulfilled passions, and a love that may have been real or imagined. The essay shows how transcreation functions as a narrative device that destabilizes the boundary between document and fiction, between private and collective memory, while offering a vivid portrayal of wartime Germany and a reflection on the creative agency of the translator, the fallibility of memory, and the transformative nature of writing. The novel ultimately emerges as a work of emotional, historical, and linguistic recomposition, asserting the enduring power of human bonds and storytelling against the forces of destruction
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Investigating molecular and regulatory boundaries of the pluripotent state
No full textAlthough progressively restricted to specialized functions during ontogeny, differentiated somatic cell nuclei can be experimentally directed to other cell types, including those with complete developmental potential. The technical challenges inherent to initial nuclear reprogramming methods such as somatic cell nuclear transfer and cell fusion pose significant hurdles to precisely dissecting the regulatory programs governing cell identity. The discovery of reprogramming via ectopic delivery of a defined set of transcription factors provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability, and pluripotency. Despite ongoing progress, a detailed molecular understanding of the terminal events that coordinate the reprogramming from somatic to pluripotent cell remains elusive. To better understand how transcription factors mediate such a dramatic change in cell state, we optimized a time course-based model where differentiating cells are systematically challenged to reacquire pluripotency. Using this approach, we identify a transient period of time after pluripotency exit where cells are developmentally determined, yet respond to induction of exogenous reprogramming factors by reverting to the pluripotent state in a near-deterministic fashion. This brief period is followed by a rapid decline into somatic-like reprogramming kinetics and efficiency. By investigating transcriptional, epigenetic, and transcription factor dynamics on either side of this window, we find several key molecular parameters that prescribe the regulatory boundary between non-pluripotent and pluripotent identities. We show that the route to pluripotency is directed through OCT4 engagement at a distinguishable subset of pluripotent-state enhancers that are uniquely regulated during differentiation in vitro and in vivo and encode a distinctive combination of cis-regulatory sequences. From these data, we present a model where delayed silencing of these enhancers predisposes them to function as primary genetic targets for the final, deterministic transition into molecular pluripotency.Medical SciencesMedical Sciencespluripotency; reprogramming; iPSC; epigenetic
Abstract 443: Lymphatic endothelium protects breast cancer cells from death by inducing metabolic adaptations
No full textAbstract
The lymphatic vasculature is an important pathway for breast cancer dissemination, yet it is not understood whether and how the lymphatic vessel microenvironment influences cancer metastasis. We demonstrate that lymphatic endothelial cells (LECs) promote survival of triple-negative breast cancer cells (TNBCs) under stress by improving mitochondrial function and inducing metabolic shift to promote cellular energy production. LECs protected TNBCs from death in vitro induced by the loss of attachment and nutrient deprivation. Cell death was preceded with a sharp increase in reactive oxygen species (ROS), strong up-regulation of Nrf2-mediated oxidative stress response genes and a rapid decline of mitochondrial activity. LECs lowered ROS levels, decreased mitochondrial superoxide formation and enhanced mitochondrial activity in TNBCs. RNAseq transcriptome analysis identified key regulator of mitochondrial metabolism and cellular bioenergetics, peroxisome proliferator-activated receptor gamma coactivator (PPARGC1A/PGC-1α, to be specifically up-regulated in breast cancer cells by LEC-derived factors. Inhibition studies demonstrated that the TNBC survival was dependent on pentose phosphate pathway (PPP) activity. Notably, LECs induced a metabolic shift from glycolysis to fatty-acid oxidation (FAO) and oxidative phosphorylation to maintain ATP and sustain cell viability. These data demonstrate that lymphatic endothelium promotes survival of breast cancer cells by regulating energy production and maintaining redox homeostasis. Our findings suggest that lymphatic endothelium may facilitate metastasis by promoting survival of breast cancer cells within the lymphatic vasculature.
Citation Format: Mirela Berisa, Simona Podgrabinska, Brandon Nicolay, Raul Mostoslavsky, Jerry Chipuk, Mihaela Skobe. Lymphatic endothelium protects breast cancer cells from death by inducing metabolic adaptations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 443. doi:10.1158/1538-7445.AM2017-443</jats:p
História e Crônica: Raul Pompéia e a série "Da Capital" * History and Chronicle: Raul Pompeia and the series "Da Capital"
No full textThis paper integrates the charts of a larger study in which we investigate the trajectory, the militancy and Raul Pompeia’s political ideals (1863-1895) placing him in the Brazilian context in late nineteenth century. We highlight, particularly, Raul Pompeia’s chronicals for the newspaper “O Estado de São Paulo in a series which the author titled "Da Capital" and was published by an afternoon newspaper from São Paulo between 1891 and 1893. We have tried to understand, through this work, how the chronicle, as a genre on the border
between literature and history, works as a documentary witness able to reveal the political
tensions of an era.O presente trabalho integra os quadros de uma pesquisa mais ampla, na qual investigamos a trajetória, a militância e os ideais políticos de Raul Pompeia (1863-1895), situando-o no contexto brasileiro do final do século XIX. Enfatizamos, particularmente, a produção cronística de Raul Pompeia para o jornal O Estado de S. Paulo em uma série que o próprio autor intitulou de “Da Capital” e que foi publicada pelo vespertino paulista entre 1891 e 1893. Procuramos compreender, por meio deste trabalho, como a crônica, enquanto gênero na fronteira entre a literatura e a história, opera como um testemunho documental capaz de revelar as tensões políticas de uma época.
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